LIQ861 (861), a novel dry powder formulation of Treprostinil (TRE) is designed to enhance deep-lung delivery and achieve higher tolerated dose levels than current inhaled pulmonary arterial hypertension (PAH) therapies.
We previous reported results from LTI-101, a placebo-controlled, double-blind, randomized, single-center study that evaluated the ascending single-dose pharmacokinetics (PK) of LIQ861 in healthy subjects.
LTI-102 was a randomized, open-label, crossover study comparing single doses of LIQ861 and Tyvaso to determine comparative bioavailability. Twenty-four subjects were randomized to one of three treatment sequences (LIQ861/LIQ861, Tyvaso/LIQ861, LIQ861/Tyvaso). Sequence 1 assessed the reproducibility of LIQ861 dosing and systemic levels of treprostinil utilizing the RS00 Dry Powder Inhaler (Plastiape, Osagno It.). Sequences 2 and 3, evaluated the rate and extent of treprostinil exposure after LIQ861 administration (nominal 75 mcg dose/ 79.5 mcg capsule strength) compared to 9 breaths (approximately 54 mcg) Tyvaso administered as per US PI1, utilizing the TD-300 nebulizer.
The LTI-101 study demonstrated, treprostinil exposure from LIQ861 increased proportionally across all doses studied (25-150 mcg). The PK profile of treprostinil administered as LIQ861 was consistent with prior Tyvaso® studies). All LIQ861 doses were generally well tolerated no deaths, serious AEs, or dose-limiting toxicities reported. In LTI-102, treatment emergent AES related to LIQ861 and Tyvaso were mild to moderate in intensity and consistent with known prostanoid effects. In sequence 1, mean LIQ861 Cmax and AUC values were comparable, confirming reproducible dose delivery. In sequences 2 and 3, Tmax and exposure parameters Cmax, AUClast, and AUCinf were similar with slightly lower values for 861 than Tyvaso. Cmax and AUC geometric mean ratios indicate treprostinil systemic exposure (dose delivered to the lung) after LIQ861 administration is > 90% of Tyvaso (Figure1).
Study LTI-102 demonstrates that LIQ861 and Tyvaso have comparable Treprostinil systemic exposures, justifying reliance on FDA’s previous finding of safety and effectiveness for Tyvaso.